11-3013840-T-C

Position:

• chr11-3013840-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001014437.3(CARS1):​c.1987-1564A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 151,652 control chromosomes in the GnomAD database, including 9,620 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.32 (9620 hom., cov: 31)
• Consequence: CARS1 NM_001014437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207

Genes affected

CARS1 (HGNC:1493): (cysteinyl-tRNA synthetase 1) This gene encodes a class 1 aminoacyl-tRNA synthetase, cysteinyl-tRNA synthetase. Each of the twenty aminoacyl-tRNA synthetases catalyzes the aminoacylation of a specific tRNA or tRNA isoaccepting family with the cognate amino acid. This gene is one of several located near the imprinted gene domain on chromosome 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian and breast cancers. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARS1	NM_001014437.3	c.1987-1564A>G		intron_variant		ENST00000380525.9	NP_001014437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARS1	ENST00000380525.9	c.1987-1564A>G		intron_variant		1	NM_001014437.3	ENSP00000369897	P3

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48454 AN: 151536 Hom.: 9610 Cov.: 31

Gnomad AFR AF: 0.0907

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.632

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.346

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.320 AC: 48478 AN: 151652 Hom.: 9620 Cov.: 31 AF XY: 0.322 AC XY: 23859 AN XY: 74124

Gnomad4 AFR AF: 0.0906

Gnomad4 AMR AF: 0.483

Gnomad4 ASJ AF: 0.412

Gnomad4 EAS AF: 0.633

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.384

Gnomad4 OTH AF: 0.350

Alfa AF: 0.368 Hom.: 5571

Bravo AF: 0.321

Asia WGS AF: 0.503 AC: 1747 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.0
DANN	Benign	0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12421922; hg19: chr11-3035070;